Distinct mechanisms for Ctr1-mediated copper and cisplatin transport.

Distinct mechanisms for Ctr1-mediated copper and cisplatin transport. Research Abstract Details 

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Distinct mechanisms for Ctr1-mediated copper and cisplatin transport. Abstract Text:

Devis Sinani,David J Adle,Heejeong Kim,Jaekwon Lee,

The Ctr1 family of integral membrane proteins is necessary for high affinity copper uptake in eukaryotes. Ctr1 is also involved in cellular accumulation of cisplatin, a platinum-based anticancer drug. Although the physiological role of Ctr1 has been revealed, the mechanism of action of Ctr1 remains to be elucidated. To gain a better understanding of Ctr1-mediated copper and cisplatin transport, we have monitored molecular dynamics and transport activities of yeast Saccharomyces cerevisiae Ctr1 and its mutant alleles. Co-expression of functional Ctr1 monomers fused with either cyan or yellow fluorescent protein resulted in fluorescence resonance energy transfer (FRET), which is consistent with multimer assembly of Ctr1. Copper near the K(m) value of Ctr1 enhanced FRET in a manner that correlated with cellular copper transport. In vitro cross-linking of Ctr1 confirmed that copper-induced FRET reflects conformational changes within pre-existing Ctr1 complexes. FRET assays in membrane-disrupted cells and protein extracts showed that intact cell structure is necessary for Ctr1 activity. Despite Ctr1-dependent cellular accumulation, cisplatin did not change Ctr1 FRET nor did it attenuate copper-induced FRET. A Ctr1 allele defective in copper transport enhanced cellular cisplatin accumulation. N-terminal methionine-rich motifs that are dispensable for copper transport play a critical role for cisplatin uptake. Taken together, our data reveal functional roles for structural remodeling of the Ctr1 multimeric complex in copper transport and suggest distinct mechanisms employed by Ctr1 for copper and cisplatin transport.

Distinct mechanisms for Ctr1-mediated copper and cisplatin transport. Publishing Authors By Initials

D Sinani,DJ Adle,H Kim,J Lee,

For similar proteins: fungal proteins: saccharomyces cerevisiae proteins research abstracts see: proteins: fungal proteins: saccharomyces cerevisiae proteins research

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Distinct mechanisms for Ctr1-mediated copper and cisplatin transport. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 26775-85

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 12

MONTH: 07

YEAR: 2007

Distinct mechanisms for Ctr1-mediated copper and cisplatin transport. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Distinct mechanisms for Ctr1-mediated copper and cisplatin transport. Keywords Mesh Terms:

KEYWORDS: Saccharomyces cerevisiae Proteins

MESH TERMS: physiology

Chemical & Substance for Abstract: Distinct mechanisms for Ctr1-mediated copper and cisplatin transport. Information

Substance Name: Copper

Registry Number: 7440-50-8

Grant and Affiliation Information for Distinct mechanisms for Ctr1-mediated copper and cisplatin transport.

AFFILIATION: Redox Biology Center, Department of Biochemistry, University of Nebraska, Lincoln, NE 68588-0664, USA.

Country: United States

AGENCY: United States NCRR

GRANT: P20 RR 17675

ACRONYM: RR

MEDLINETA: J Biol Chem

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